A Phase 2, 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
Overview
- Phase
- Phase 2
- Intervention
- SM04690
- Conditions
- Knee Osteoarthritis
- Sponsor
- Biosplice Therapeutics, Inc.
- Enrollment
- 700
- Locations
- 1
- Primary Endpoint
- Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This phase 2 study is a placebo-controlled, double-blind, parallel group study of four concentrations of SM04690 (0.03, 0.07, 0.15, and 0.23 mg per 2 mL injection) injected intraarticularly (IA) into the target knee joint of subjects with moderately to severely symptomatic osteoarthritis (OA). Based on previous studies of SM04690, key phenotypes of laterality (unilateral vs bilateral) as well as chronic pain (as measured by the Widespread Pain Index) were identified as confounding variables impacting the overall assessment of both radiologic and clinical efficacy outcomes. The design of SM04690-OA-04 is based upon previous study designs while assessing strategies to combat the confounding impact of laterality and chronic pain. To evaluate the effect of IA vehicle injection on patient-reported outcomes (PRO) such as pain, stiffness, and function in OA, this study also includes one cohort that receives a 2 mL IA injection of vehicle (placebo), and one cohort that receives a sham injection (i.e., a needle stick with 0 mL vehicle injected).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ambulatory
- •Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at screening (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
- •Pain compatible with OA of the knee(s) for at least 26 weeks prior to screening
- •Primary source of pain throughout the body is due to OA in the target knee
- •Willingness to use an electronic diary on a daily basis in the evening for the screening period and 24-week study duration
- •Negative drug test for opioids and drugs of abuse, except alcohol and marijuana, at screening
- •Subjects with depression or anxiety must be clinically stable for 12 weeks prior to screening, and, if on treatment for depression or anxiety, be on 12 weeks of stable therapy
- •Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
- •Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed
Exclusion Criteria
- •Women who are pregnant, lactating, or have a positive pregnancy result at screening
- •Women of child bearing potential who are sexually active and are not willing to use a highly effective method of birth control during the study period
- •Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized or whom are not using a highly effective method of birth control
- •Body mass index (BMI) \> 35
- •Partial or complete joint replacement in either knee
- •Currently requires regular use of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches) or use of a lower extremity prosthesis, and/or a structural knee brace
- •Previous participation in a Samumed clinical trial investigating SM04690
- •Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to screening
- •Any planned surgery during the study period
- •History of malignancy within the last 5 years; however, subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible if completely excised. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years prior to any study injection
Arms & Interventions
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
Intervention: SM04690
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
Intervention: SM04690
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
Intervention: SM04690
0.23 mg SM04690
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
Intervention: SM04690
Placebo
Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle
Intervention: Placebo
Sham
Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle
Intervention: Sham
Outcomes
Primary Outcomes
Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)
Time Frame: Baseline and Week 24
Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 24. The pain NRS is an 11-point scale \[0-10\] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain (pain as bad as one can imagine).
Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)
Time Frame: Baseline and Week 24
Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 24. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore is standardized and reported ranging from 0 to 100 \[0 = no pain; 100 = pain as bad as it can be\].
Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
Time Frame: Baseline and Week 24
Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 24. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore is standardized and reported ranging from 0 to 100 \[0 = no functional disability, 100 = unable to function\].
Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee
Time Frame: Baseline and Week 24
Change from baseline in mJSW as documented by radiograph of the target knee.
Secondary Outcomes
- Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)(Baseline and Week 24)